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1.
Folia Histochem Cytobiol ; 57(4): 159-167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31746453

RESUMO

INTRODUCTION: The extremely-low frequency electromagnetic field (ELFEMF) has been proposed for use in cancer therapy since it was found that magnetic waves interfere with many biological processes. Gold nanoparticles (Au-NPs) have been widely used for drug delivery during cancer in vitro studies due to their low cytotoxity and high biocompatibility. The electroporation of cancer cells in a presence of Au-NPs (EP Au-NPs) can induce cell apoptosis, alterations of cell cycle profile and morphological changes. The impact of ELFEMF and EP Au-NPs on morphology, cell cycle and activation of apoptosis-associated genes on Hep-2 laryngeal cancer cell line has not been studied yet. MATERIALS AND METHODS: ELFEMF on Hep-2 cells were carried out using four different conditions: 25/50 mT at 15/30 min, while Au-NPs were used as direct contact (DC) or with electroporation (EP, 10 pulses at 200V, equal time intervals of 4 sec). MTT assay was used to check the toxicity of DC Au-NPs. Expression of CASP3, P53, BAX and BCL2 genes was quantified using qPCR. Cell cycle was analyzed by flow cytometry. Hematoxylin and eosin (HE) staining was used to observe cell morphology. RESULTS: Calculated IC50 of DC Au-NPs 24.36 µM (4.79 µg/ml) and such concentration was used for further DC and EP AuNPs experiments. The up-regulation of pro-apoptotic genes (CASP3, P53, BAX) and decreased expression of BCL2, respectively, was observed for all analyzed conditions with the highest differences for EP AuNPs and ELFEMF 50 mT/30 min in comparison to control cells. The highest content of cells arrested in G2/M phase was observed in ELFEMF-treated cells for 30 min both at 25 or 50 mT, while the cells treated with EP AuNPs or ELFEMF 50 mT/15 min showed highest ratios of apoptotic cells. HE staining of electroporated cells and cells exposed to ELFEMF's low and higher frequencies for different times showed nuclear pleomorphic cells. Numerous apoptotic bodies were observed in the irregular cell membrane of neoplastic and necrotic cells with mixed euchromatin and heterochromatin. CONCLUSIONS: Our observations indicate that treatment of Hep-2 laryngeal cancer cells with ELFEMF for 30 min at 25-50 mT and EP Au-NPs can cause cell damage inducing apoptosis and cell cycle arrest.


Assuntos
Antineoplásicos/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Campos Eletromagnéticos , Eletroporação/métodos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/toxicidade , Regulação para Cima
2.
Appl Biochem Biotechnol ; 189(3): 709-728, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31602558

RESUMO

Dense brush conformation-bearing theranostic agents are emerging as drug delivery systems due to their higher ability to escape from reticuloendothelial system uptake which prolongs their in vivo circulation time. With the aim of developing dual therapy agent, 13-nm gold nanoparticles' (AuNPs) surfaces were coated with different amounts of polyethylene glycol (PEG) (SH-PEG-NH2) to obtain dense brush conformation-bearing theranostic agents. Among the 14 different theranostic agent candidates prepared, the one hosting 1819 PEG per particle was selected as the most promising theranostic agent candidate based on structural conformation, stability, size, zeta potential, hemocompatibility, cell inhibition, and cell death pathway towards MCF-7 cell line. To test drug delivery efficiency of the developed PEGylated AuNP and to improve efficacy of the treatment, apoptotic peptide (AP) was covalently conjugated to NH2 terminus of the PEG in various ratios to yield AuNP-AP conjugate. Among the prepared conjugates, the one having 1 nmol of peptide per milliliter of AuNP yielded the most promising results based on the same criteria as employed for PEGylated AuNPs. Besides, incorporation of AP to AuNP returned in superior efficacy of AP since it was possible to achieve 50% cell death with 1000 times less amount of AP alone.


Assuntos
Portadores de Fármacos/química , Ouro/química , Nanopartículas Metálicas , Nanomedicina Teranóstica , Morte Celular/efeitos dos fármacos , Ácido Cítrico/química , Portadores de Fármacos/toxicidade , Ouro/toxicidade , Hemólise/efeitos dos fármacos , Humanos , Células MCF-7 , Conformação Molecular , Tamanho da Partícula , Polietilenoglicóis/química
3.
Int J Nanomedicine ; 14: 7643-7663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571869

RESUMO

Angiogenesis is the formation of new blood vessels from pre-existing vessels. It is a highly regulated process as determined by the interplay between pro-angiogenic and anti-angiogenic factors. Under certain conditions the balance between angiogenesis stimulators and inhibitors is altered, which results in a shift from physiological to pathological angiogenesis. Therefore, the goal of therapeutic targeting of angiogenic process is to normalize vasculature in target tissues by enhancing angiogenesis in disease conditions of reduced vascularity and blood flow, such as tissue ischemia, or alternatively to inhibit excessive and abnormal angiogenesis in disorders like cancer. Gold nanoparticles (AuNPs) are special particles that are generated by nanotechnology and composed of an inorganic core containing gold which is encircled by an organic monolayer. The ability of AuNPs to alter vasculature has captured recent attention in medical literature as potential therapeutic agents for the management of pathologic angiogenesis. This review provides an overview of the effects of AuNPs on angiogenesis and the molecular mechanisms and biomedical applications associated with their effects. In addition, the main synthesis methods, physical properties, uptake mechanisms, and toxicity of AuNPs are briefly summarized.


Assuntos
Tecnologia Biomédica/métodos , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Endocitose , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/toxicidade
4.
Aquat Toxicol ; 215: 105287, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31491706

RESUMO

Gold nanoparticles are used as drug delivery vectors based on the assumption that they have low toxicity. Literature has, however, produced conflicting results over the last few years. As such, this study aimed to investigate the toxicological effects of nanogold (nAu) on several indicators that range from subcellular to whole-organism level. Gene regulation, changes in oxidative stress biomarkers and swimming performance were assessed in Danio rerio (zebrafish) following exposures to nAu. Adult zebrafish were exposed in vivo to nAu for 96 h and swimming performance measured post-exposure. Liver tissue was collected for DNA microarray and Real-Time Polymerase Chain Reactions (RT-PCR) analyses to determine changes in gene expression (catalase, superoxide dismutase and metallothioneins) and protein biomarker analyses (catalase, superoxide dismutase, acetylcholine esterase, malondialdehyde, cellular energy allocation and metallothionein) were performed on whole-body samples. Swimming behaviour was assessed in 1.1 L Tecniplast™ tanks for a period of six hours and videos were analysed using Noldus EthoVision software. Critical swimming speed was measured in a Loligo® swimming tunnel. The DNA microarray revealed that fish exposed to 20 mg/L differed most from the control group. At 20 mg/L there was a significant increase in gene expression for all genes analysed but this didn't translate to significant responses in protein biomarker levels except for an increase in protein carbonyl formation. The behaviour results demonstrated significant changes in distance moved, swimming speed, acceleration bouts, zone alterations and time spent within the top zone - responses that are usually observed in fish responding to toxicological stress. Furthermore, the critical swimming speed of exposed fish was decreased significantly compared to the control. Since swimming performance and social interaction among zebrafish is essential to their survival, whole-organism behaviour that suggests a toxicological response after exposure to nAu is in agreement with the genetic responses measured in this study.


Assuntos
Comportamento Animal/efeitos dos fármacos , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Peixe-Zebra/fisiologia , Animais , Biomarcadores/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Nanopartículas Metálicas/ultraestrutura , Família Multigênica , Músculos/efeitos dos fármacos , Natação , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética
5.
Nanoscale ; 11(28): 13458-13468, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31287475

RESUMO

The large number of nanomaterial-based applications emerging in the materials and life sciences and the foreseeable increasing use of these materials require methods that evaluate and characterize the toxic potential of these nanomaterials to keep safety risks to people and environment as low as possible. As nanomaterial toxicity is influenced by a variety of parameters like size, shape, chemical composition, and surface chemistry, high throughput screening (HTS) platforms are recommended for assessing cytotoxicity. Such platforms are not yet available for genotoxicity testing. Here, we present first results obtained for application-relevant nanomaterials using an automatable genotoxicity platform that relies on the quantification of the phosphorylated histone H2AX (γ-H2AX) for detecting DNA double strand breaks (DSBs) and the automated microscope system AKLIDES® for measuring integral fluorescence intensities at different excitation wavelengths. This platform is used to test the genotoxic potential of 30 nm-sized citrate-stabilized gold nanoparticles (Au-NPs) as well as micellar encapsulated iron oxide nanoparticles (FeOx-NPs) and different cadmium (Cd)-based semiconductor quantum dots (QDs), thereby also searching for positive and negative controls as reference materials. In addition, the influence of the QD shell composition on the genotoxic potential of these Cd-based QDs was studied, using CdSe cores as well as CdSe/CdS core/shell and CdSe/CdS/ZnS core/shell/shell QDs. Our results clearly revealed the genotoxicity of the Au-NPs and its absence in the FeOx-NPs. The genotoxicity of the Cd-QDs correlates with the shielding of their Cd-containing core, with the core/shell/shell architecture preventing genotoxicity risks. The fact that none of these nanomaterials showed cytotoxicity at the chosen particle concentrations in a conventional cell viability assay underlines the importance of genotoxicity studies to assess the hazardous potential of nanomaterials.


Assuntos
Cádmio/química , Histonas/metabolismo , Testes de Mutagenicidade/métodos , Nanoestruturas/toxicidade , Pontos Quânticos/química , Cádmio/toxicidade , Sobrevivência Celular , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Compostos Férricos/química , Compostos Férricos/toxicidade , Fluorometria , Ouro/química , Ouro/toxicidade , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Testes de Mutagenicidade/instrumentação , Nanoestruturas/química , Tamanho da Partícula , Fosforilação/efeitos dos fármacos , Pontos Quânticos/toxicidade
6.
Talanta ; 204: 44-49, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357318

RESUMO

Bacillus cereus, a common soil bacterium, has been shown to act as a biogeochemical indicator for concealed mineralisations, e.g., vein-type Au deposits. Field and cultivation-free detection of Bacillus cereus in the presence of Au3+ and other metal ions is significantly important but still almost blank in current biogeochemical prospecting of gold mine system. Herein, a self-established simple approach was slightly improved to make silver nanoparticles (Ag NPs) rapidly concentrated on every bacterial cell, and highly strong and distinct surface-enhanced Raman scattering (SERS) signals of Bacillus cereus free from any native fluorescence have been obtained in a so called 'mixing-and-measuring' manner. Furthermore, SERS was used for the first time to our knowledge to investigate the impacts of different concentrations of metal ions on Bacillus cereus, and successfully utilized for distinguishing Au3+ ions from other species. A more convincing multi-Raman criterion based on Raman bands, and further the entire Raman spectrum in combination with statistical analysis (e.g., principal component analysis (PCA)) were found capable of detecting spectral differences of Bacillus cereus in the presence of metal ions (Au3+, Ag+, Cu2+ and Zn2+) with different concentrations. An interesting phenomenon has been found that except for Au3+ ions, the highest permissive concentration of other metal ions for the detected Bacillus cereus is up to 10 µg/mL possibly due to their resistance to Au. The results also indicate that an effective biogeochemical exploration technique of SERS spectral response may be developed, where Bacillus cereus spore counts are measured in the field and used as a pre-screening method to target areas useful for further sampling and complete geochemical analysis.


Assuntos
Bacillus cereus/isolamento & purificação , Carga Bacteriana/métodos , Ouro/farmacologia , Bacillus cereus/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ouro/química , Ouro/toxicidade , Nanopartículas Metálicas/química , Mineração/métodos , Análise de Componente Principal , Prata/química , Análise Espectral Raman/métodos , Esporos Bacterianos/efeitos dos fármacos , Esporos Bacterianos/isolamento & purificação
7.
Talanta ; 204: 548-554, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357332

RESUMO

In this paper, a new strategy was presented for fluorescence labeling and imaging Al3+ in live cells with excess aluminum ions using thiolated fluorescence gold nanoclusters (Au NCs). The glutathione (GSH)-capped Au NCs were prepared via a green, facile one-pot method in aqueous solution and displayed excellent stability, ultrasmall size, monodispersity, and larger Stokes shift, which exhibits a relatively weak fluorescence at 650 nm Al3+-induced fluorescence enhancement of the GSH-Au NCs can be observed due to Al3+-triggered aggregation-induced emission (AIE) effect, which allows the role of GSH-Au NCs as a fluorescence light-up probe for detection of Al3+. Moreover, it was demonstrated that the fluorescence probe for Al3+ showed a wide detection range from 100 to 600 µM and good selectivity against other metal ions and common biomolecule. Furthermore, due to the advantages of excellent biocompatibility, low toxicity, red emission and high specificity, the proposed GSH-Au NCs fluorescence probes are suitable for the imaging of high concentrations of aluminum ions in cells, which can be applied to the diagnosis of cellular aluminum poisoning.


Assuntos
Alumínio/análise , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Glutationa/química , Ouro/química , Nanopartículas Metálicas/química , Linhagem Celular , Fluorescência , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Glutationa/toxicidade , Ouro/efeitos da radiação , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/efeitos da radiação , Nanopartículas Metálicas/toxicidade , Raios Ultravioleta
8.
Ecotoxicol Environ Saf ; 181: 60-68, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31174108

RESUMO

The widespread use of microplastics and nanomaterials resulting in environmental contamination is of high concern. Microplastics have been found to modulate the toxicity of other environmental contaminants. Thus, the hypothesis that microplastics increase the toxicity of gold nanoparticles to the marine microalgae Tetraselmis chuii was tested. In a laboratory bioassay, T. chuii cultures were exposed for 96 h to ∼5 nm diameter gold nanoparticles (AuNP) and to virgin 1-5 µm diameter microplastics (MP), alone and in mixture. The treatments were: control; citrate-control; AuNP alone (0.1, 0.3 and 3 mg/L); MP alone (0.3, 0.9 and 4 mg/L) and mixture of the two substances in three different concentrations (0.1 mg/L AuNP + 0.3 mg/L MP; 0.3 mg/L AuNP + 0.9 mg/L MP; 3 mg/l AuNP + 4 mg/L MP). The effect criterion was the inhibition of the average specific growth rate. AuNP alone and MP alone did not cause significant decrease of T. chui average specific growth rate up to 3 mg/L and 4 mg/L, respectively. The mixture containing 3 mg/L AuNP + 4 mg/L MP significantly reduced the average specific growth rate of the microalgae. Therefore, this mixture was more toxic to T. chuii than its components individually. Overall, the results of the present study indicated that the MP and AuNP tested have a relatively low toxicity to T. chuii, but the toxicity increases when they are in mixtures containing high concentrations of both substances. These proof-of-concept findings stress the need of more research on the toxicity of mixtures containing microplastics and nanomaterials.


Assuntos
Clorófitas/efeitos dos fármacos , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Microalgas/efeitos dos fármacos , Plásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Bioensaio , Modelos Teóricos
9.
Toxicol In Vitro ; 58: 170-177, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30928693

RESUMO

This research reports on the cytotoxicity of materials present in a wound biosensor on human keratinocytes (HaCaT) to evaluate the biocompatibility of the sensor for continuous wound monitoring applications. Individual and collective effects of the sensor materials, gold (Au) and silver (Ag) nanoparticles (NPs), uricase enzyme (UOx), ferrocene carboxylic acid (FCA), multi-walled carbon nanotubes (MWCNTs) and poly vinyl alcohol-based polymer (PVA-SbQ) on HaCaT were studied. The toxicology profiles of these materials were derived from cell viability, mitochondrial activity retention and apoptotic behavior studies. At the concentrations present in the sensor, the cell viability studies showed minimal toxicity for Au and Ag NPs, UOx and FCA (cell viability >75%), while MWCNTs and PVA-SbQ exhibited excellent biocompatibility towards keratinocytes (cell viability >90%). Resazurin assay confirmed minimal impairment of mitochondrial activity at lower concentrations for all the materials (mitochondrial activity >0.7). The caspase-3/7 apoptotic assay showed no pronounced apoptotic behavior caused by the materials. The material mixtures studied were Au/UOx/FCA/PVA-SbQ, Ag/UOx/FCA/PVA-SbQ, and MWCNTs/UOx/FCA/PVA-SbQ. A higher toxicity profile was observed for the heterogeneous material mixtures as a result of the cumulative effect of the individual materials. However, the biosensor itself was seen to exhibit lower toxicity (~5%) compared to the material mixtures, due to the protective PVA-SbQ capping over the biosensor. This work establishes the biocompatibility of the reported wound sensor for human measurements with minimal toxic effects on human keratinocytes.


Assuntos
Compostos Ferrosos/toxicidade , Ouro/toxicidade , Queratinócitos/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Nanotubos de Carbono/toxicidade , Álcool de Polivinil/toxicidade , Prata/toxicidade , Urato Oxidase/toxicidade , Técnicas Biossensoriais , Catálise , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Metalocenos , Ferimentos e Lesões
10.
Colloids Surf B Biointerfaces ; 179: 56-65, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30947084

RESUMO

One hallmark of solid tumors, regardless of its type or stage, is the existence of an unsual acidic microenvironment, which has been considered a specific and ideal target for cancer imaging. Therefore, we developed a pH-activatable nanoprobe GNPs-CKL-FA for near-infrared fluorescence (NIR) and computed tomography (CT) imaging of tumors. This nanoprobe consists of a near-infrared fluorophore (Cy5.5), a pH-sensitive ketal linker, and gold nanoparticles (GNPs) decorated with folates that could bind to tumor cells' surface receptors to promote cellular internalization. This ability of folate to mediate tumor targeting and accelerate internalization has been confirmed by in vitro experiments with HeLa cells. The fluorescence of the nanoprobes successfully activated by low intracellular pH, especially in more acidic organelles. Furthermore, fluorescence signals increased to a greater extent when the pH in tumors was lowered by injection of acetate buffer and isoproterenol. The CT contrast of GNPs-CKL-FA was obtained after administering intravenously to HeLa subcutaneous tumor-bearing mice. These results suggest that GNPs-CKL-FA has the potential to be a pH-activatable fluorescent nanoprobe combined with CT contrast agent for tumor targeted imaging.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Neoplasias/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho , Tomografia Computadorizada por Raios X , Células A549 , Animais , Carbocianinas/química , Morte Celular , Ácido Fólico/química , Ouro/toxicidade , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/ultraestrutura , Camundongos Endogâmicos BALB C , Camundongos Nus , Ácido Tióctico/química , Distribuição Tecidual/efeitos dos fármacos
11.
Environ Toxicol Pharmacol ; 68: 4-12, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30849701

RESUMO

In the field of nanoecotoxicology, very few reports have focused on biochemical changes in non-target organisms after nanoexposure. A less explored aquatic non-target crustacean, Moina macrocopa, was used in the present study to analyze toxicity effects of gold nanoparticles (AuNPs), an emerging nanomaterial. AuNPs was fabricated using tannic acid and were 29 ± 2 nm in size. The 48 h LC50 value of AuNPs was 14 ± 0.14 mg/L against M. macrocopa. The sub-lethal exposure of M. macrocopa juveniles to AuNPs (1.47 and 2.95 mg/L) decreased the activities of acetyl cholinesterase and digestive enzymes (trypsin and amylase). A concentration dependant increase in the activities of antioxidant enzymes such as catalase, superoxide dismutase and glutathione S-transferase suggested the generation of oxidative stress in M. macrocopa after AuNPs exposure. Changes in enzyme activity can be utilized as biomarker(s) for early detection of nanoparticle contamination in aquatic habitat. AuNPs accumulation in gut of M. macrocopa increased the metal bio burden (11 mg/L) and exhibited inhibitory action on digestive enzymes. Complete depuration of AuNPs was not observed after transferring nano-exposed M. macrocopa to normal medium without AuNPs. AuNPs tended to adhere on external body parts such as setae, carapace of M. macrocopa which interfered with swimming activity and also changed the behavioral pattern. AuNPs underwent agglomeration in the medium used for maintenance of M. macrocopa. As nanomaterials are emerging pollutants in aquatic systems, the present work highlights the hazardous effect of AuNPs and development of enzymatic biomarkers to curtail it at community level.


Assuntos
Cladóceros/efeitos dos fármacos , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Amilases/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Catalase/metabolismo , Cladóceros/fisiologia , Glutationa Transferase/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Dose Letal Mediana , Superóxido Dismutase/metabolismo , Testes de Toxicidade/métodos , Tripsina/metabolismo
12.
Ann Agric Environ Med ; 26(1): 198-202, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30922053

RESUMO

INTRODUCTION: Various Acanthamoeba species are free-living organisms widely distributed in the human environment. Amphizoic amoebae as facultative parasites may cause vision-threatening eye disease - Acanthamoeba keratitis, mostly among contact lens wearers. As the number of cases is increasing, and applied therapy often unsuccessful, proper hygienic measures and effective contact lenses disinfection are crucial for the prevention of this disease. Available contact lens solutions are not fully effective against amphizoic amoebae; there is a need to enhance their disinfecting activity to prevent amoebic infections. The use of developing nanotechnology methods already applied with success in the prevention, diagnostic and therapy of other infectious diseases might be helpful regarding amoebic keratitis. This study assesses the in vitro effect of selected contact lens solutions conjugated with nanoparticles against Acanthamoeba trophozoites. MATERIAL AND METHODS: Three selected contact lens solutions conjugated with silver and gold nanoparticles in concentration of 0.25-2.5 ppm were used in vitro against the axenically cultured ATCC 30010 type Acanthamoeba castellanii strain. The anti-amoebic efficacy was examined based on the oxido-reduction of AlamarBlue. The cytotoxicity tests based on the measurement of lactate dehydrogenase (LDH) activity were performed using a fibroblast HS-5 cell line. RESULTS: Enhancement of the anti-amoebic activity of contact lens solutions conjugated with selected nanoparticles expressed in the dose dependent amoebic growth inhibition with a low cytotoxicity profile was observed. CONCLUSIONS: Results of the study showed that conjugation of selected contact lens solutions with silver nanoparticles might be a promising approach to prevent Acanthamoeba keratitis among contact lens users.


Assuntos
Acanthamoeba castellanii/efeitos dos fármacos , Soluções para Lentes de Contato/farmacologia , Nanopartículas Metálicas/uso terapêutico , Ceratite por Acanthamoeba/prevenção & controle , Linhagem Celular Tumoral , Soluções para Lentes de Contato/toxicidade , Ouro/farmacologia , Ouro/toxicidade , Humanos , L-Lactato Desidrogenase/metabolismo , Nanopartículas Metálicas/toxicidade , Prata/farmacologia , Prata/toxicidade , Trofozoítos/efeitos dos fármacos
13.
J Nanobiotechnology ; 17(1): 21, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30709404

RESUMO

BACKGROUND: Emerging concepts for designing innovative drugs (i.e., novel generations of antimicrobials) frequently include nanostructures, new materials, and nanoparticles (NPs). Along with numerous advantages, NPs bring limitations, partly because they can limit the analytical techniques used for their biological and in vivo validation. From that standpoint, designing innovative drug delivery systems requires advancements in the methods used for their testing and investigations. Considering the well-known ability of resazurin-based methods for rapid detection of bacterial metabolisms with very high sensitivity, in this work we report a novel optimization for tracking bacterial growth kinetics in the presence of NPs with specific characteristics, such as specific optical properties. RESULTS: Arginine-functionalized gold composite (HAp/Au/arginine) NPs, used as the NP model for validation of the method, possess plasmonic properties and are characterized by intensive absorption in the UV/vis region with a surface plasmon resonance maximum at 540 nm. Due to the specific optical properties, the NP absorption intensively interferes with the light absorption measured during the evaluation of bacterial growth (optical density; OD600). The results confirm substantial nonspecific interference by NPs in the signal detected during a regular turbidity study used for tracking bacterial growth. Instead, during application of a resazurin-based method (Presto Blue), when a combination of absorption and fluorescence detection is applied, a substantial increase in the signal-to-noise ratio is obtained that leads to the improvement of the accuracy of the measurements as verified in three bacterial strains tested with different growth rates (E. coli, P. aeruginosa, and S. aureus). CONCLUSIONS: Here, we described a novel procedure that enables the kinetics of bacterial growth in the presence of NPs to be followed with high time resolution, high sensitivity, and without sampling during the kinetic study. We showed the applicability of the Presto Blue method for the case of HAp/Au/arginine NPs, which can be extended to various types of metallic NPs with similar characteristics. The method is a very easy, economical, and reliable option for testing NPs designed as novel antimicrobials.


Assuntos
Bactérias/crescimento & desenvolvimento , Técnicas Biossensoriais/métodos , Nanoestruturas/química , Bactérias/efeitos dos fármacos , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/normas , Ouro/química , Ouro/toxicidade , Indicadores e Reagentes , Cinética , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Nanomedicina , Nanoestruturas/toxicidade , Oxazinas , Razão Sinal-Ruído , Ressonância de Plasmônio de Superfície , Xantenos
14.
Int J Nanomedicine ; 14: 951-962, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30787609

RESUMO

Background: Gastric cancer is the fourth most common cancer and second leading cause of cancer death worldwide. Cardiospermum halicacabum is used to treat nerve disorders, stiffness, rheumatism, ear ache, snake bite, and so on. Methods: In this study, the reaction parameters were optimized to control the size of the nanoparticle, which was confirmed by transmission electron microscopy. Various characterization techniques such as selected area diffraction pattern, UV-visible spectroscopy, energy-dispersive X-ray analysis, dynamic light scattering, Fourier-transform infrared spectroscopy, and atomic force microscopy were employed to analyze the synthesized AuNPs obtained from C. halicacabum (CH-AuNP) against gastric carcinoma cell line. Results: The cytotoxic effect of CH-AuNP against AGS, SNU-5, and SNU-16 cell lines was detected by MTT assay. The induction of apoptosis by CH-AuNP in AGS was analyzed by double staining technique using TUNEL and DAPI staining assays. Further to confirm the molecular mechanism exhibited by CH-AuNP to induce apoptosis, the intracellular ROS level was assessed and immunoblotting was performed to assess the apoptotic signaling molecules that often deregulated in cancerous condition. Conclusion: The results clearly prove that CH-AuNP increases ROS and induces apoptosis in AGS, suggesting that CH-AuNP may be an effective anticancer drug with no side effects to treat gastric cancer.


Assuntos
Apoptose , Caspases/metabolismo , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Sapindaceae/química , Neoplasias Gástricas/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Difusão Dinâmica da Luz , Ouro/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Neoplasias Gástricas/tratamento farmacológico
15.
Aquat Toxicol ; 208: 71-79, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30639746

RESUMO

Nanoparticle decoration with noble metal represents a promising alternative to improve their photocatalytic and photovoltaic properties. However, toxicity can be influenced by such modification, as the bioavailability of these substances may be influenced. To understand how decoration influences the NP impacts in marine ecosystems, we exposed suspension-feeding clams, Ruditapes decussatus, to two photocatalyst nanocomposites, TiO2 NPs and AuTiO2 NPs, over 2 concentrations, 50 µg L-1and 100 µg L-1, in a laboratory experiment. Accumulation of Au and Ti in gills and digestive gland was noted in clams after exposure to TiO2 NPs and AuTiO2 NPs using inductively coupled plasma optic emission spectroscopy (ICP-OES). TiO2 and AuTiO2 NPs alter the behavior of the clams Ruditapes decussatus by reducing filtration and respiration rates. Furthermore, the highest concentration of TiO2NPs induces an overproduction of H2O2 in gills and digestive gland and NO production only in gills. Superoxide dismutase (SOD), Catalase (CAT), Glutathione-S-transferase (GST) and acetylcholinesterase (AChE) activities were induced in gills and digestives gland in concentration and nanocomposite type dependent manner. Decorated form presented higher Malondialdehyde (MDA) levels in gills and digestive gland than the undecorated form, suggesting different mechanisms of action that may be mediated through oxidative stress. In conclusion, the considered parameters could represent reliable biomarkers for the assessment of NP toxicity on R. decussatus as biological biomonitoring model. In addition, based on the obtained results, nanoparticle decoration influences the toxicity of metal nanoparticles in marine organism.


Assuntos
Comportamento Animal/efeitos dos fármacos , Bivalves/metabolismo , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Nanocompostos/toxicidade , Titânio/toxicidade , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Bivalves/efeitos dos fármacos , Catalase/metabolismo , Catálise , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Peróxido de Hidrogênio/metabolismo , Luz , Malondialdeído/metabolismo , Nanopartículas Metálicas/ultraestrutura , Nanocompostos/ultraestrutura , Neurotoxinas/toxicidade , Óxido Nítrico/metabolismo , Poluentes Químicos da Água/toxicidade
16.
Int J Nanomedicine ; 14: 639-647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30697047

RESUMO

Background: Gold nanoparticles (GNPs) and their functional derivatives are of great interest because of their many biomedical applications. GNPs are increasingly being incorporated into new diagnostic and therapeutic approaches in medicine. Consequently, there has been a strong push to fully understand their interactions with blood components. The agglomeration of cells reflects the interaction of nanoparticles with blood components. Methods: The main aim of this study was to compare the effects of poly-ethylene-glycol (PEG)-oated and uncoated GNPs on the generation of reactive oxygen species (ROS); on the actions of distinct hepatotoxicity biomarkers such as alanine (ALT) and aspartate (AST) aminotransferases, and alkaline phosphatase (ALP); and on the histology of liver tissues in the rat model. Four distinct doses of PEG-coated and uncoated GNPs (12.5, 25, 50, and 100 µg/kg body weight) were used. Each group consisted of three rats receiving an oral administration of PEG-coated and uncoated GNPs for 5 days with one dose per 24 hours. The control group consisted of three rats that received deionized water. Twenty-four hours after the last treatment, samples were collected following standard procedures. Results: PEG-coated and uncoated GNPs enhanced the generation of ROS and the activity of serum aminotransferases (ALT/AST) and ALPs relative to the negative control. A liver histology assessment of GNP-exposed rats revealed statistically significant responses in the variation of the morphologies of tissues relative to those of the negative control. Nonetheless, uncoated GNPs demonstrated enhanced hepatotoxic outcomes relative to those of PEG-coated GNPs. The results demonstrated that both GNPs may be able to promote hepatotoxicity in Sprague Dawley rats through mechanisms of oxidative stress. However, uncoated GNPs have more harmful effects than PEG-coated GNPs relative to the negative control. Conclusion: Taken together, the results of this study indicate that PEG-coated GNPs may be safer to use in nanomedicinal applications than uncoated GNPs. However, more studies must be performed to confirm the outcomes of PEGylation.


Assuntos
Ouro/toxicidade , Fígado/patologia , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Polietilenoglicóis/química , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Biomarcadores/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
17.
Talanta ; 195: 197-203, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30625532

RESUMO

Biological thiols (biothiols), such as glutathione (GSH), cysteine (Cys) and homocysteine (Hcy), play a vital role in the process of reversible redox reactions in physiological systems. In this work, flow cytometry-based fluorescent sensor is for the first time developed for the detection of biothiols in a fluorescence "turn on" manner. The probe which we name "Polystyrene/Quantum Dots/Gold Nanoparticles" or (PS/QDs/Au) is constructed by immobilizing QDs onto the surface of PS microbeads to obtain fluorescent microbeads. The probe (PS/QDs/Au) is constructed by immobilizing QDs onto the surface of PS microbeads to obtain fluorescent microbeads, followed by gold NPs absorption through electrostatic interaction to quench their fluorescence. In the presence of biothiols, the fluorescence of our probe can be restored in less than 5 min, and the detection limits for GSH, Cys and Hcy are 0.5 µM, 0.1 µM and 0.3 µM, respectively. Most importantly, the fluorescence signal of each of our probe microbeads can be collected individually by flow cytometry, realizing single microbead-based biothiols detection for the first time. Moreover, the probe is successfully applied to imaging of intracellular biothiols in A549 cells, demonstrating its potential in biological application.


Assuntos
Cisteína/análise , Corantes Fluorescentes/química , Glutationa/análise , Homocisteína/análise , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Cisteína/química , Citometria de Fluxo , Fluorescência , Corantes Fluorescentes/toxicidade , Glutationa/química , Ouro/química , Ouro/toxicidade , Homocisteína/química , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Microesferas , Poliestirenos/química , Poliestirenos/toxicidade , Pontos Quânticos/química , Pontos Quânticos/toxicidade
18.
Nanoscale ; 11(7): 3173-3185, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30534785

RESUMO

As nano- and micro-sized plastics accumulate in the environment and the food chain of animals, including humans, it is imperative to assess the effects of nanoplastics in living organisms in a systematic manner, especially because of their ability to adsorb potential toxicants such as pollutants, heavy metals, and organic macromolecules that coexist in the environment. Using the zebrafish embryo as an animal model, we investigated the bioaccumulation and in vivo toxicity of polystyrene (PS) nanoplastics individually or in combination with the Au ion. We showed that smaller PS nanoplastics readily penetrated the chorion and developing embryos and accumulated throughout the whole body, mostly in lipid-rich regions such as in yolk lipids. We also showed that PS nanoplastics induced only marginal effects on the survival, hatching rate, developmental abnormalities, and cell death of zebrafish embryos but that these effects were synergistically exacerbated by the Au ion in a dose- and size-dependent manner. Such exacerbation of toxicity was well correlated with the production of reactive oxygen species and the pro-inflammatory responses synergized by the presence of PS, supporting the combined toxicity of PS and Au ions. The synergistic effect of PS on toxicity appeared to relate to mitochondrial damage as determined by ultrastructural analysis. Taken together, the effects of PS nanoplastics were marginal but could be a trigger for exacerbating the toxicity induced by other toxicants such as metal ions.


Assuntos
Embrião não Mamífero/metabolismo , Ouro/toxicidade , Nanopartículas/toxicidade , Poliestirenos/toxicidade , Peixe-Zebra/metabolismo , Animais , Embrião não Mamífero/patologia , Íons/toxicidade
19.
Chemosphere ; 220: 11-19, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30576896

RESUMO

Due to their diverse applications, gold nanoparticles (AuNPs) are expected to increase of in the environment, although few studies are available on their mode of action in aquatic organisms. The genotoxicity of AuNPs, alone or combined with the human pharmaceutical gemfibrozil (GEM), an environmental contaminant frequently detected in aquatic systems, including in marine ecosystems, was examined using gilthead seabream erythrocytes as a model system. Fish were exposed for 96 h to 4, 80 and 1600 µg L-1 of 40 nm AuNPs with two coatings - citrate or polyvinylpyrrolidone; GEM (150 µg L-1); and a combination of AuNPs and GEM (80 µg L-1 AuNPs + 150 µg L-1 GEM). AuNPs induced DNA damage and increased nuclear abnormalities levels, with coating showing an important role in the toxicity of AuNPs to fish. The combined exposures of AuNPs and GEM produced an antagonistic response, with observed toxic effects in the mixtures being lower than the predicted. The results raise concern about the safety of AuNPs and demonstrate interactions between them and other contaminants.


Assuntos
Dano ao DNA/efeitos dos fármacos , Genfibrozila/toxicidade , Nanopartículas Metálicas/toxicidade , Mutagênicos , Animais , Organismos Aquáticos , Interações de Medicamentos , Eritrócitos/efeitos dos fármacos , Ouro/toxicidade , Humanos , Dourada/sangue , Dourada/fisiologia
20.
Med Res Rev ; 39(1): 302-327, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29766541

RESUMO

Many research projects are underway to improve the diagnosis and therapy in ophthalmology. Indeed, visual acuity deficits affect 285 million people worldwide and different strategies are being developed to strengthen patient care. One of these strategies is the use of gold nanoparticles (GNP) for their multiple properties and their ability to be used as both diagnosis and therapy tools. This review exhaustively details research developing GNPs for use in ophthalmology. The toxicity of GNPs and their distribution in the eye are described through in vitro and in vivo studies. All publications addressing the pharmacokinetics of GNPs administered in the eye are extensively reviewed. In addition, their use as biosensors or for imaging with optical coherence tomography is illustrated. The future of GNPs for ophthalmic therapy is also discussed. GNPs can be used to deliver genes or drugs through different administration routes. Their antiangiogenic and anti-inflammatory properties are of great interest for different ocular pathologies. Finally, GNPs can be used to improve stereotactic radiosurgery, brachytherapy, and photothermal therapy because of their many properties.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Oftalmologia , Animais , Sistemas de Liberação de Medicamentos , Olho/efeitos dos fármacos , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/ultraestrutura
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